CA2290707C - Animaux transgeniques dans lesquels l'expression de l'apolipoproteine e est alteree et procedes de dosage associes - Google Patents
Animaux transgeniques dans lesquels l'expression de l'apolipoproteine e est alteree et procedes de dosage associes Download PDFInfo
- Publication number
- CA2290707C CA2290707C CA002290707A CA2290707A CA2290707C CA 2290707 C CA2290707 C CA 2290707C CA 002290707 A CA002290707 A CA 002290707A CA 2290707 A CA2290707 A CA 2290707A CA 2290707 C CA2290707 C CA 2290707C
- Authority
- CA
- Canada
- Prior art keywords
- human
- apoe
- apoe4
- apoe3
- apolipoprotein
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 230000009261 transgenic effect Effects 0.000 title claims abstract description 63
- 101710095339 Apolipoprotein E Proteins 0.000 title claims abstract description 43
- 102100029470 Apolipoprotein E Human genes 0.000 title claims abstract description 36
- 241001465754 Metazoa Species 0.000 title abstract description 74
- 238000003556 assay Methods 0.000 title description 18
- 241000282414 Homo sapiens Species 0.000 claims abstract description 108
- 238000000034 method Methods 0.000 claims abstract description 58
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 58
- 108700019146 Transgenes Proteins 0.000 claims abstract description 30
- 108010029485 Protein Isoforms Proteins 0.000 claims abstract description 27
- 102000001708 Protein Isoforms Human genes 0.000 claims abstract description 27
- 101000771674 Homo sapiens Apolipoprotein E Proteins 0.000 claims abstract description 10
- 102000053020 human ApoE Human genes 0.000 claims abstract description 9
- 101150037123 APOE gene Proteins 0.000 claims description 172
- 101100216294 Danio rerio apoeb gene Proteins 0.000 claims description 149
- 210000004027 cell Anatomy 0.000 claims description 58
- 230000000694 effects Effects 0.000 claims description 56
- 239000003795 chemical substances by application Substances 0.000 claims description 53
- 230000006870 function Effects 0.000 claims description 45
- 210000002569 neuron Anatomy 0.000 claims description 31
- 230000001537 neural effect Effects 0.000 claims description 25
- 238000012360 testing method Methods 0.000 claims description 23
- 238000012216 screening Methods 0.000 claims description 22
- 241000124008 Mammalia Species 0.000 claims description 19
- 238000004458 analytical method Methods 0.000 claims description 16
- 108091026890 Coding region Proteins 0.000 claims description 14
- 239000002773 nucleotide Substances 0.000 claims description 14
- 125000003729 nucleotide group Chemical group 0.000 claims description 14
- 230000004075 alteration Effects 0.000 claims description 13
- 230000004770 neurodegeneration Effects 0.000 claims description 12
- 239000013543 active substance Substances 0.000 claims description 11
- 210000001787 dendrite Anatomy 0.000 claims description 11
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 claims description 11
- 230000031836 visual learning Effects 0.000 claims description 11
- 108010060159 Apolipoprotein E4 Proteins 0.000 claims description 10
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 claims description 9
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 claims description 9
- 210000001320 hippocampus Anatomy 0.000 claims description 9
- 210000000478 neocortex Anatomy 0.000 claims description 9
- 210000000063 presynaptic terminal Anatomy 0.000 claims description 9
- 230000003920 cognitive function Effects 0.000 claims description 7
- 230000015654 memory Effects 0.000 claims description 7
- 210000004962 mammalian cell Anatomy 0.000 claims description 6
- 108700028369 Alleles Proteins 0.000 claims description 5
- 108010060215 Apolipoprotein E3 Proteins 0.000 claims description 4
- 102000008128 Apolipoprotein E3 Human genes 0.000 claims description 4
- 238000012347 Morris Water Maze Methods 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 abstract description 16
- 238000011820 transgenic animal model Methods 0.000 abstract description 8
- 230000007170 pathology Effects 0.000 abstract description 7
- 230000001404 mediated effect Effects 0.000 abstract description 5
- 238000002560 therapeutic procedure Methods 0.000 abstract description 5
- 241000699670 Mus sp. Species 0.000 description 105
- 230000014509 gene expression Effects 0.000 description 44
- 210000004556 brain Anatomy 0.000 description 31
- 102000004169 proteins and genes Human genes 0.000 description 22
- 230000027455 binding Effects 0.000 description 20
- 239000003814 drug Substances 0.000 description 20
- 235000018102 proteins Nutrition 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 230000013016 learning Effects 0.000 description 19
- 210000001519 tissue Anatomy 0.000 description 18
- 238000011830 transgenic mouse model Methods 0.000 description 18
- 239000000523 sample Substances 0.000 description 17
- 230000006735 deficit Effects 0.000 description 16
- 230000006399 behavior Effects 0.000 description 15
- 108020004414 DNA Proteins 0.000 description 14
- 210000003169 central nervous system Anatomy 0.000 description 14
- 241000699666 Mus <mouse, genus> Species 0.000 description 13
- 241000699660 Mus musculus Species 0.000 description 13
- 238000010171 animal model Methods 0.000 description 13
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 13
- 229940079593 drug Drugs 0.000 description 13
- 239000003153 chemical reaction reagent Substances 0.000 description 12
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 12
- 239000002953 phosphate buffered saline Substances 0.000 description 12
- 108091028043 Nucleic acid sequence Proteins 0.000 description 11
- 238000001514 detection method Methods 0.000 description 11
- 108020004999 messenger RNA Proteins 0.000 description 11
- 150000007523 nucleic acids Chemical class 0.000 description 11
- 230000000384 rearing effect Effects 0.000 description 11
- 230000008859 change Effects 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 238000007634 remodeling Methods 0.000 description 10
- 238000011282 treatment Methods 0.000 description 10
- 238000012217 deletion Methods 0.000 description 9
- 230000037430 deletion Effects 0.000 description 9
- 230000001419 dependent effect Effects 0.000 description 9
- 230000002068 genetic effect Effects 0.000 description 9
- 208000014674 injury Diseases 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 8
- 230000006378 damage Effects 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 208000028867 ischemia Diseases 0.000 description 8
- 150000002632 lipids Chemical class 0.000 description 8
- 108020004707 nucleic acids Proteins 0.000 description 8
- 102000039446 nucleic acids Human genes 0.000 description 8
- 238000003752 polymerase chain reaction Methods 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- 230000008439 repair process Effects 0.000 description 8
- 239000013598 vector Substances 0.000 description 8
- 238000001262 western blot Methods 0.000 description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 7
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 7
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 230000003542 behavioural effect Effects 0.000 description 7
- 210000005013 brain tissue Anatomy 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 230000001771 impaired effect Effects 0.000 description 7
- 210000002241 neurite Anatomy 0.000 description 7
- 229920001184 polypeptide Polymers 0.000 description 7
- 238000011084 recovery Methods 0.000 description 7
- 230000009182 swimming Effects 0.000 description 7
- 208000037259 Amyloid Plaque Diseases 0.000 description 6
- 206010012289 Dementia Diseases 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 206010008118 cerebral infarction Diseases 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 210000001428 peripheral nervous system Anatomy 0.000 description 6
- 238000007423 screening assay Methods 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 238000013258 ApoE Receptor knockout mouse model Methods 0.000 description 5
- 201000006474 Brain Ischemia Diseases 0.000 description 5
- 206010008120 Cerebral ischaemia Diseases 0.000 description 5
- 230000010558 Gene Alterations Effects 0.000 description 5
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 5
- 208000014633 Retinitis punctata albescens Diseases 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 230000000692 anti-sense effect Effects 0.000 description 5
- 210000002459 blastocyst Anatomy 0.000 description 5
- 230000001149 cognitive effect Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 230000003961 neuronal insult Effects 0.000 description 5
- 108091006146 Channels Proteins 0.000 description 4
- 108010010234 HDL Lipoproteins Proteins 0.000 description 4
- 102000015779 HDL Lipoproteins Human genes 0.000 description 4
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 4
- 102000004895 Lipoproteins Human genes 0.000 description 4
- 108090001030 Lipoproteins Proteins 0.000 description 4
- 108700026244 Open Reading Frames Proteins 0.000 description 4
- 229930040373 Paraformaldehyde Natural products 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 210000003050 axon Anatomy 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 229960002685 biotin Drugs 0.000 description 4
- 235000020958 biotin Nutrition 0.000 description 4
- 239000011616 biotin Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 210000000349 chromosome Anatomy 0.000 description 4
- 239000003623 enhancer Substances 0.000 description 4
- 210000004602 germ cell Anatomy 0.000 description 4
- 238000009396 hybridization Methods 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 230000010354 integration Effects 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 229930014626 natural product Natural products 0.000 description 4
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 4
- 230000007991 neuronal integrity Effects 0.000 description 4
- 229920002866 paraformaldehyde Polymers 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000011808 rodent model Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 108010067770 Endopeptidase K Proteins 0.000 description 3
- 241000283074 Equus asinus Species 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101100055865 Homo sapiens APOE gene Proteins 0.000 description 3
- 101100055876 Mus musculus Apoe gene Proteins 0.000 description 3
- 239000000020 Nitrocellulose Substances 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 108090001076 Synaptophysin Proteins 0.000 description 3
- 102000004874 Synaptophysin Human genes 0.000 description 3
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 230000006736 behavioral deficit Effects 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 238000009395 breeding Methods 0.000 description 3
- 230000001488 breeding effect Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000002744 homologous recombination Methods 0.000 description 3
- 230000006801 homologous recombination Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 206010027175 memory impairment Diseases 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 229920001220 nitrocellulos Polymers 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 150000002894 organic compounds Chemical class 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 102000013415 peroxidase activity proteins Human genes 0.000 description 3
- 108040007629 peroxidase activity proteins Proteins 0.000 description 3
- 210000004129 prosencephalon Anatomy 0.000 description 3
- 230000006798 recombination Effects 0.000 description 3
- 238000005215 recombination Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- 230000000472 traumatic effect Effects 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 102000007592 Apolipoproteins Human genes 0.000 description 2
- 108010071619 Apolipoproteins Proteins 0.000 description 2
- 108090001008 Avidin Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 208000031942 Late Onset disease Diseases 0.000 description 2
- 102000001851 Low Density Lipoprotein Receptor-Related Protein-1 Human genes 0.000 description 2
- 108010015340 Low Density Lipoprotein Receptor-Related Protein-1 Proteins 0.000 description 2
- 208000026139 Memory disease Diseases 0.000 description 2
- 102000029749 Microtubule Human genes 0.000 description 2
- 108091022875 Microtubule Proteins 0.000 description 2
- 102000015636 Oligopeptides Human genes 0.000 description 2
- 108010038807 Oligopeptides Proteins 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- 235000004789 Rosa xanthina Nutrition 0.000 description 2
- 241000109329 Rosa xanthina Species 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 101710195626 Transcriptional activator protein Proteins 0.000 description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000009692 acute damage Effects 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 239000003593 chromogenic compound Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 238000004624 confocal microscopy Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 230000010102 embolization Effects 0.000 description 2
- 210000002257 embryonic structure Anatomy 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 238000003205 genotyping method Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- 210000005154 hemibrain Anatomy 0.000 description 2
- 230000006951 hyperphosphorylation Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 238000007901 in situ hybridization Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 208000037906 ischaemic injury Diseases 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 210000004688 microtubule Anatomy 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 230000000116 mitigating effect Effects 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 230000008450 motivation Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000005709 nerve cell growth Effects 0.000 description 2
- 239000003176 neuroleptic agent Substances 0.000 description 2
- 230000002981 neuropathic effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 239000002831 pharmacologic agent Substances 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- 238000010149 post-hoc-test Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 238000002601 radiography Methods 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000003345 scintillation counting Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000006886 spatial memory Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- -1 tracheal lavage Substances 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 230000009529 traumatic brain injury Effects 0.000 description 2
- 230000001720 vestibular Effects 0.000 description 2
- 108700026220 vif Genes Proteins 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 102000013918 Apolipoproteins E Human genes 0.000 description 1
- 108010025628 Apolipoproteins E Proteins 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- 108091028026 C-DNA Proteins 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010008089 Cerebral artery occlusion Diseases 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- 238000006711 Chan reduction reaction Methods 0.000 description 1
- 206010061764 Chromosomal deletion Diseases 0.000 description 1
- 108010004103 Chylomicrons Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 238000012287 DNA Binding Assay Methods 0.000 description 1
- 108020003215 DNA Probes Proteins 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 101100259947 Homo sapiens TBATA gene Proteins 0.000 description 1
- 101000679903 Homo sapiens Tumor necrosis factor receptor superfamily member 25 Proteins 0.000 description 1
- 201000010252 Hyperlipoproteinemia Type III Diseases 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- 239000012741 Laemmli sample buffer Substances 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 102000011965 Lipoprotein Receptors Human genes 0.000 description 1
- 108010061306 Lipoprotein Receptors Proteins 0.000 description 1
- 108091027974 Mature messenger RNA Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101000771687 Mus musculus Apolipoprotein E Proteins 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 1
- 102000005891 Pancreatic ribonuclease Human genes 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 208000010886 Peripheral nerve injury Diseases 0.000 description 1
- 241000577979 Peromyscus spicilegus Species 0.000 description 1
- 108010089430 Phosphoproteins Proteins 0.000 description 1
- 102000007982 Phosphoproteins Human genes 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 101001058233 Rattus norvegicus Gamma-enolase Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 239000012163 TRI reagent Substances 0.000 description 1
- KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102100022203 Tumor necrosis factor receptor superfamily member 25 Human genes 0.000 description 1
- 206010060751 Type III hyperlipidaemia Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000002009 allergenic effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000003941 amyloidogenesis Effects 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000001796 anti-degenerative effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 208000013404 behavioral symptom Diseases 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 210000004952 blastocoel Anatomy 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 201000008247 brain infarction Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 1
- 229960001076 chlorpromazine Drugs 0.000 description 1
- 101150087654 chrnd gene Proteins 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 230000009693 chronic damage Effects 0.000 description 1
- 210000003703 cisterna magna Anatomy 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 230000003931 cognitive performance Effects 0.000 description 1
- 238000009226 cognitive therapy Methods 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 1
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 1
- RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 1
- NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000000385 dialysis solution Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
- 229960005156 digoxin Drugs 0.000 description 1
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 238000007878 drug screening assay Methods 0.000 description 1
- 210000001951 dura mater Anatomy 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000003027 ear inner Anatomy 0.000 description 1
- 238000002337 electrophoretic mobility shift assay Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000004077 genetic alteration Effects 0.000 description 1
- 231100000118 genetic alteration Toxicity 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000002149 gonad Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 description 1
- ZJYYHGLJYGJLLN-UHFFFAOYSA-N guanidinium thiocyanate Chemical compound SC#N.NC(N)=N ZJYYHGLJYGJLLN-UHFFFAOYSA-N 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 208000020887 hyperlipoproteinemia type 3 Diseases 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000007786 learning performance Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000003715 limbic system Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 230000004576 lipid-binding Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 208000018883 loss of balance Diseases 0.000 description 1
- 230000004777 loss-of-function mutation Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000004630 mental health Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 201000007309 middle cerebral artery infarction Diseases 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000001423 neocortical effect Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 210000005044 neurofilament Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000014511 neuron projection development Effects 0.000 description 1
- 230000005015 neuronal process Effects 0.000 description 1
- 210000004179 neuropil Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 210000000869 occipital lobe Anatomy 0.000 description 1
- 235000019645 odor Nutrition 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 208000027232 peripheral nervous system disease Diseases 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229940124606 potential therapeutic agent Drugs 0.000 description 1
- 235000008476 powdered milk Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 230000013777 protein digestion Effects 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 210000002763 pyramidal cell Anatomy 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000007261 regionalization Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 230000028527 righting reflex Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 210000004116 schwann cell Anatomy 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 238000012764 semi-quantitative analysis Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004960 subcellular localization Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 210000001138 tear Anatomy 0.000 description 1
- 229960002784 thioridazine Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000007862 touchdown PCR Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960001005 tuberculin Drugs 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 230000003936 working memory Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0276—Knock-out vertebrates
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/775—Apolipopeptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2207/00—Modified animals
- A01K2207/15—Humanized animals
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
- A01K2267/0318—Animal model for neurodegenerative disease, e.g. non- Alzheimer's
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/035—Animal model for multifactorial diseases
- A01K2267/0356—Animal model for processes and diseases of the central nervous system, e.g. stress, learning, schizophrenia, pain, epilepsy
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Environmental Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Wood Science & Technology (AREA)
- Biodiversity & Conservation Biology (AREA)
- Animal Husbandry (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
Cette invention concerne des modèles d'animaux transgéniques non humains utilisés pour étudier le fonctionnement génique, l'animal transgénique se caractérisant par le fait qu'il présente un fonctionnement génique altéré de l'apolipoprotéine E endogène et un transgène pour l'isoforme d'apolipoprotéine E humaine endogène. Les animaux transgéniques peuvent être homozygotes ou hétérozygotes pour le transgène. Cette invention concerne également des procédés d'utilisation des modèles d'animaux transgéniques non humains pour étudier les pathologies induites par l'apolipoprotéine E et pour identifier des composés et des thérapies destinées à ces mêmes pathologies.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/070,670 | 1998-04-30 | ||
| US09/070,670 US6046381A (en) | 1998-04-30 | 1998-04-30 | Apolipoprotein E transgenic mice and assay methods |
| PCT/US1999/009531 WO1999055852A1 (fr) | 1998-04-30 | 1999-04-29 | Animaux transgeniques dans lesquels l'expression de l'apolipoproteine e est alteree et procedes de dosage associes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2290707A1 CA2290707A1 (fr) | 1999-11-04 |
| CA2290707C true CA2290707C (fr) | 2007-02-13 |
Family
ID=22096690
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002290707A Expired - Fee Related CA2290707C (fr) | 1998-04-30 | 1999-04-29 | Animaux transgeniques dans lesquels l'expression de l'apolipoproteine e est alteree et procedes de dosage associes |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US6046381A (fr) |
| EP (1) | EP1005542B1 (fr) |
| JP (1) | JP2002507898A (fr) |
| AT (1) | ATE315085T1 (fr) |
| AU (1) | AU747691B2 (fr) |
| CA (1) | CA2290707C (fr) |
| DE (1) | DE69929324T2 (fr) |
| WO (1) | WO1999055852A1 (fr) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7964598B2 (en) * | 1995-10-17 | 2011-06-21 | The J. David Gladstone Institutes | ApoE4 domain interaction inhibitors and methods of use thereof |
| US7129061B1 (en) * | 1996-08-07 | 2006-10-31 | Biogen Idec Ma Inc. | Tumor necrosis factor related ligand |
| WO2000042073A1 (fr) | 1999-01-15 | 2000-07-20 | Biogen, Inc. | Antagonistes de la proteine tweak et du recepteur de tweak, et leur utilisation pour traiter des affections immunitaires |
| JP2002539458A (ja) * | 1999-03-16 | 2002-11-19 | セレックス， インコーポレイテッド | 唾液中のａｐｏａおよびａｐｏｂ、ならびにそれらの比を検出するための方法およびデバイス |
| US6982361B1 (en) * | 2000-02-25 | 2006-01-03 | The Regents Of The University Of California | Method of screening a compound for anxiolytic activity in an Apolipoprotein e knockout animal |
| WO2002014492A2 (fr) * | 2000-08-14 | 2002-02-21 | Iogenetics, Llc | Bovins resistant au syndrome de la vache grasse |
| WO2002026107A2 (fr) * | 2000-09-25 | 2002-04-04 | The Regents Of The University Of California | Modele de maladies neurodegeneratives impliquant une accumulation de substances amyloides |
| WO2002030454A1 (fr) * | 2000-10-13 | 2002-04-18 | University Of Cincinnati | Procedes de regulation de la lyse de sang coagule au moyen d'un phenotype d'apolipoproteine e4 |
| AU2002214644A1 (en) * | 2000-10-13 | 2002-04-22 | University Of Cincinnati | Methods for enhancing lysing of coagulated blood with apolipoprotein e2 phenotype |
| CA2426030C (fr) * | 2000-11-03 | 2013-12-31 | The J. David Gladstone Institutes | Procedes de traitement des maladies liees a l'apolipoproteine e |
| US7081561B2 (en) * | 2001-03-16 | 2006-07-25 | The Regents Of The University Of California | Gene-targeted animal model of apolipoprotein E4 domain interaction and uses thereof |
| JP2003055266A (ja) * | 2001-06-04 | 2003-02-26 | Univ Texas Syst | Ｍｅｋ５ならびに心臓肥大および拡張型心筋症に関連する方法および組成物 |
| US20040092013A1 (en) * | 2001-08-14 | 2004-05-13 | Snyder Evan Y. | Method of treating alzheimer's disease with cell therapy |
| CA2887716C (fr) | 2002-04-09 | 2017-01-24 | Biogen Idec Ma Inc. | Procede pour traiter les etats lies a tweak |
| WO2004006662A1 (fr) * | 2002-07-15 | 2004-01-22 | Takeda Pharmaceutical Company Limited | Animal modele de maladie portant un gene etranger ppar$g(a) transfere et utilisation correspondante |
| US7432355B2 (en) | 2002-08-09 | 2008-10-07 | The J. David Gladstone Institutes | Apolipoprotein E stable folding intermediate and methods of use thereof |
| US7297836B2 (en) | 2003-03-24 | 2007-11-20 | The J. David Gladstone Institutes | Methods of detecting neurological disorders |
| US7056286B2 (en) | 2003-11-12 | 2006-06-06 | Adrian Ravenscroft | Medical device anchor and delivery system |
| US7612179B2 (en) | 2003-11-28 | 2009-11-03 | Astrazeneca Ab | antibodies binding to a C-terminal fragment of apoliopoprotein E |
| WO2005051998A2 (fr) | 2003-11-28 | 2005-06-09 | Astrazeneca Ab | Anticorps |
| US7579224B2 (en) * | 2005-01-21 | 2009-08-25 | Semiconductor Energy Laboratory Co., Ltd. | Method for manufacturing a thin film semiconductor device |
| AU2006214179A1 (en) | 2005-02-17 | 2006-08-24 | Biogen Idec Ma Inc. | Treating neurological disorders |
| EP1885388B1 (fr) | 2005-05-10 | 2013-09-11 | Biogen Idec MA Inc. | Traitement et evaluation des troubles inflammatoires |
| WO2006138219A2 (fr) | 2005-06-13 | 2006-12-28 | Biogen Idec Ma Inc. | Procedes d'evaluation de patients |
| JP5055293B2 (ja) * | 2005-12-07 | 2012-10-24 | ザ ジェイ． デヴィッド グラッドストーン インスティテューツ | ミトコンドリア機能を調節する物質を同定する方法 |
| US20090082271A1 (en) * | 2005-12-07 | 2009-03-26 | Mahley Robert W | Agents that reduce apoe-induced impairment of mitochondria and methods of use thereof |
| US20090136456A1 (en) * | 2006-12-22 | 2009-05-28 | Yadong Huang | Methods of treating neurodegenerative disorders |
| US10092427B2 (en) | 2009-11-04 | 2018-10-09 | Confluent Medical Technologies, Inc. | Alternating circumferential bridge stent design and methods for use thereof |
| WO2012047308A1 (fr) | 2010-10-08 | 2012-04-12 | Nitinol Devices And Components, Inc. | Autre conception d'endoprothèse vasculaire de pont circonférentielle et ses procédés d'utilisation |
| US11957115B2 (en) | 2017-03-21 | 2024-04-16 | The Jackson Laboratory | Genetically modified mouse expressing human APOE4 and mouse Trem2 p.R47H and methods of use thereof |
| US20220099659A1 (en) * | 2019-01-23 | 2022-03-31 | The Regents Of The University Of California | Human Genomic Construct Reporter Cells and Mouse Models to Screen Therapeutics against Microglia-expressed Disease Associated Genes |
| CN110684765A (zh) * | 2019-09-20 | 2020-01-14 | 浙江大学 | 痴呆相关致病基因捕获探针的筛选方法、捕获基因组和产品及应用 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3343530A1 (de) * | 1983-12-01 | 1985-06-13 | Max Planck Gesellschaft | Arzneimittel mit verbesserter penetration der gewebsmembran |
| US5017566A (en) * | 1987-12-30 | 1991-05-21 | University Of Florida | Redox systems for brain-targeted drug delivery |
| US5002935A (en) * | 1987-12-30 | 1991-03-26 | University Of Florida | Improvements in redox systems for brain-targeted drug delivery |
| WO1994013798A1 (fr) * | 1992-12-16 | 1994-06-23 | Bergmann Johanna E | Agents destines a la prophylaxie et au traitement de la maladie d'alzheimer chez l'homme |
| WO1995006470A1 (fr) * | 1993-08-30 | 1995-03-09 | Merck & Co., Inc. | Prevention et traitement de la maladie d'alzheimer |
| DE69433243T2 (de) * | 1993-08-31 | 2004-07-29 | Duke University | Verwendunf von ApoE zum Binden von TAU und MAP2c Proteinen und zur Behandlung von Alzheimer's Krankheit |
| JP2001517065A (ja) * | 1995-06-07 | 2001-10-02 | アセナ ニューロサイエンシーズ，インコーポレイテッド | トランスジェニック動物モデルを用いてアルツハイマー病治療薬を同定する方法 |
| US5767337A (en) * | 1995-07-31 | 1998-06-16 | Duke University | Creation of human apolipoprotein E isoform specific transgenic mice in apolipoprotein deficient "knockout" mice |
-
1998
- 1998-04-30 US US09/070,670 patent/US6046381A/en not_active Expired - Lifetime
-
1999
- 1999-04-29 AT AT99920236T patent/ATE315085T1/de not_active IP Right Cessation
- 1999-04-29 JP JP55461299A patent/JP2002507898A/ja active Pending
- 1999-04-29 AU AU37781/99A patent/AU747691B2/en not_active Ceased
- 1999-04-29 EP EP99920236A patent/EP1005542B1/fr not_active Expired - Lifetime
- 1999-04-29 CA CA002290707A patent/CA2290707C/fr not_active Expired - Fee Related
- 1999-04-29 DE DE69929324T patent/DE69929324T2/de not_active Expired - Lifetime
- 1999-04-29 WO PCT/US1999/009531 patent/WO1999055852A1/fr active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| AU747691B2 (en) | 2002-05-16 |
| EP1005542A1 (fr) | 2000-06-07 |
| CA2290707A1 (fr) | 1999-11-04 |
| DE69929324D1 (de) | 2006-03-30 |
| ATE315085T1 (de) | 2006-02-15 |
| WO1999055852A1 (fr) | 1999-11-04 |
| US6046381A (en) | 2000-04-04 |
| DE69929324T2 (de) | 2006-09-28 |
| EP1005542A4 (fr) | 2003-05-14 |
| AU3778199A (en) | 1999-11-16 |
| EP1005542B1 (fr) | 2006-01-04 |
| JP2002507898A (ja) | 2002-03-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2290707C (fr) | Animaux transgeniques dans lesquels l'expression de l'apolipoproteine e est alteree et procedes de dosage associes | |
| US6175057B1 (en) | Transgenic mouse model of alzheimer's disease and cerebral amyloid angiopathy | |
| Von Koch et al. | Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice | |
| CA2127450C (fr) | Modeles d'animaux transgeniques pour la maladie d'alzheimer | |
| US7186881B2 (en) | Testing compounds for effects on synaptophysin in transgenic mice expressing an Alzheimer's disease FAD DNA sequence | |
| US6211428B1 (en) | Transgenic mouse expressing a familial form of human amyloid precursor protein | |
| US6187992B1 (en) | Transgenic mouse having a disrupted amyloid precursor protein gene | |
| JP2000513929A (ja) | 進行性神経疾患を有するトランスジェニック非ヒト哺乳動物 | |
| JPH09511388A (ja) | 進行性神経疾患を持つヒト以外のトランスジェニック哺乳類 | |
| JP2001517065A (ja) | トランスジェニック動物モデルを用いてアルツハイマー病治療薬を同定する方法 | |
| US7057086B2 (en) | Therapeutic methods employing PAI-1 inhibitors and transgenic non-human animal for screening candidate PAI-1 inhibitors | |
| US6455757B1 (en) | Transgenic mice expressing human APP and TGF-β demonstrate cerebrovascular amyloid deposits | |
| JP2001514528A (ja) | 天然プレセニリン１ヌルバックグラウンド上で非天然野生型および家族性アルツハイマー病突然変異プレセニリン１タンパク質を発現するトランスジェニック動物 | |
| JPH11507821A (ja) | トランスジェニック動物モデルを用いてアルツハイマー病治療薬を同定する方法 | |
| US20060230466A1 (en) | Gene-targeted animal model of apolipoprotein E4 domain interaction and uses thereof | |
| WO1998019714A1 (fr) | Souris proteiniquement carencee en adenine de translocation nucleotidique myocardiale | |
| US8502016B1 (en) | Genomic alpha synuclein transgenic animal | |
| US8993833B2 (en) | Model of Alzheimer's Disease | |
| WO2013016826A1 (fr) | Modèle animal non-humain transgénique d'une maladie neurodégénérative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20180430 |